PMC:5097349 / 14302-15863 JSONTXT

{"project":"AxD_symptoms","denotations":[{"id":"T67","span":{"begin":107,"end":123},"obj":"Phenotype"},{"id":"T68","span":{"begin":159,"end":164},"obj":"Phenotype"}],"attributes":[{"id":"A67","pred":"hp_id","subj":"T67","obj":"http://purl.obolibrary.org/obo/HP_0100320"},{"id":"A68","pred":"hp_id","subj":"T68","obj":"http://purl.obolibrary.org/obo/HP_0031273"}],"text":"Mutations in the GFAP gene, which lead to the accumulation of ubiquitinated intracytoplasmic inclusions in rosenthal fibers in association with the small heat shock proteins, HSP27 and aB-crystallin [1], are thought to account for more than 95 % of AxD cases [24]. In infantile [3, 25, 26], juvenile [20, 27] and sporadic adult AxD [28–30], the heterozygous missense mutation of the GFAP gene, c.1246C \u003e T, p.R416W, has been reported to be one of the causes of AxD. While In familial adult onset AxD it has been rarely reported. Thyagarajan described a woman and her son with adult onset AxD and the above mutation [31]. They had different clinical manifestations but strikingly similar MRI abnormalities and the same GFAP mutation. It means that molecularly characterized inherited AxD is a cause of symptoms. The same GFAP mutation can cause both early and late onset AxD, and vertical transmission occurs in adult onset AxD with GFAP mutations. Our patient, her mother and maternal aunt had similar neurological manifestations but the latter two had a relative later onset. Nevertheless, her mother’s clinical manifestations deteriorated rapidly, her maternal aunt has mild symptoms with comparatively slow progress. She and her daughter had the same heterozygous missense mutation. All these findings suggest that the familial Adult AxD members can possibly show either similar or different manifestations. The molecular genetic evidence of our AxD family favors that AxD is an autosomal dominant inheritance [32], but further long-term follow-up is needed."}

{"project":"2_test","denotations":[{"id":"27814755-8393618-12819202","span":{"begin":200,"end":201},"obj":"8393618"},{"id":"27814755-22496548-12819203","span":{"begin":260,"end":262},"obj":"22496548"},{"id":"27814755-11138011-12819204","span":{"begin":279,"end":280},"obj":"11138011"},{"id":"27814755-1407707-12819205","span":{"begin":282,"end":284},"obj":"1407707"},{"id":"27814755-9025838-12819206","span":{"begin":286,"end":288},"obj":"9025838"},{"id":"27814755-12034785-12819207","span":{"begin":301,"end":303},"obj":"12034785"},{"id":"27814755-15732097-12819208","span":{"begin":305,"end":307},"obj":"15732097"},{"id":"27814755-17894839-12819209","span":{"begin":333,"end":335},"obj":"17894839"},{"id":"27814755-16505300-12819209","span":{"begin":333,"end":335},"obj":"16505300"},{"id":"27814755-14550921-12819209","span":{"begin":333,"end":335},"obj":"14550921"},{"id":"27814755-15390001-12819210","span":{"begin":616,"end":618},"obj":"15390001"},{"id":"27814755-13665382-12819211","span":{"begin":1514,"end":1516},"obj":"13665382"}],"text":"Mutations in the GFAP gene, which lead to the accumulation of ubiquitinated intracytoplasmic inclusions in rosenthal fibers in association with the small heat shock proteins, HSP27 and aB-crystallin [1], are thought to account for more than 95 % of AxD cases [24]. In infantile [3, 25, 26], juvenile [20, 27] and sporadic adult AxD [28–30], the heterozygous missense mutation of the GFAP gene, c.1246C \u003e T, p.R416W, has been reported to be one of the causes of AxD. While In familial adult onset AxD it has been rarely reported. Thyagarajan described a woman and her son with adult onset AxD and the above mutation [31]. They had different clinical manifestations but strikingly similar MRI abnormalities and the same GFAP mutation. It means that molecularly characterized inherited AxD is a cause of symptoms. The same GFAP mutation can cause both early and late onset AxD, and vertical transmission occurs in adult onset AxD with GFAP mutations. Our patient, her mother and maternal aunt had similar neurological manifestations but the latter two had a relative later onset. Nevertheless, her mother’s clinical manifestations deteriorated rapidly, her maternal aunt has mild symptoms with comparatively slow progress. She and her daughter had the same heterozygous missense mutation. All these findings suggest that the familial Adult AxD members can possibly show either similar or different manifestations. The molecular genetic evidence of our AxD family favors that AxD is an autosomal dominant inheritance [32], but further long-term follow-up is needed."}